Method for non-synchronous laser-assisted transmyocardial revascularization

ABSTRACT

A method of selecting laser parameters for performing laser-assisted transmyocardial revascularization (TMR) to avoid inducing undesired cardiac arrhythmia without synchronization of delivery of laser energy and the patient&#39;s cardiac cycle, the method comprising the steps of minimizing the power level of laser energy used, thereby decreasing the overall trauma to the heart, selecting a pulse frequency as great as possible while avoiding adverse summation effects, selecting a pulse width as wide as possible to prevent excessively high peak powers per pulse and not so wide as to cause undesired thermal damage, selecting an energy flux rate, shaping the front end of each pulse of laser energy to provide efficient, non explosive TMR channeling, and correcting the selected power level, pulse width, pulse frequency and energy flux rate for mechanical events, including method of access to the heart, position of selected portions of myocardium in the heart, temporal duration of the procedure, natural movement of the heart, specific heart geometry, pre-existing heart arrhythmia and other factors causing a predisposition to heart arrhythmia. A method for performing laser-assisted transmyocardial revascularization (TMR) using such laser energy with parameters selected to avoid inducing undesired cardiac arrhythmia, the method comprising the steps of generating laser energy having a predetermined non-square wave shape, a predetermined wavelength, a predetermined energy flux and a predetermined power level, and delivering the laser energy in a plurality of pulses, the plurality of pulses having a predetermined pulse frequency and a predetermined pulse width, to selected portions of myocardium to form TMR channels in myocardium without synchronizing delivery of the laser beam with the cardiac cycle.

FIELD OF THE INVENTION

The present invention relates to a procedure known as laser-assistedtransmyocardial revascularization (TMR), and more particularly, to animproved method for revascularization of the heart by creating aplurality of small pathways or channels through predetermined portionsof the heart using laser energy delivered via a laser delivery meansaccording to specific parameters, including variable frequency, andwithout requiring synchronization of laser energy delivery with thebeating of the heart.

BACKGROUND OF THE INVENTION

Much of the heart consists of a special type of muscle calledmyocardium. The myocardium requires a constant supply of oxygen andnutrients to allow it to contract and pump blood throughout thevasculature. One method of improving reduced myocardial blood supply iscalled transmyocardial revascularization (TMR), the creation of pathwaysor channels into the myocardium generally from either an outerepicardial surface of the heart in a surgical procedure or from an innerendothelium cell covered surface of a heart chamber in a percutaneousprocedure.

A procedure using needles in a form of "myocardial acupuncture" was usedclinically in the 1960s. Deckelbaum. L. I., Cardiovascular Applicationsof Laser Technology, Lasers in Surgery and Medicine 15:315-341 (1994).The technique was said to relieve ischemia by allowing blood to passfrom the ventricle through the channels either directly into othervessels perforated by the channels or into myocardial sinusoids whichconnect to the myocardial microcirculation. These sinusoidalcommunications vary in size and structure, but represent a network ofdirect arterial-luminal, arterial-arterial, arterial-venous, andvenous-luminal connections. Interest in myocardial acupuncture orboring, which mechanically displaces or removes tissue, decreased whenit was discovered that the mechanically created channels closed becauseof acute thrombosis followed by organization and fibrosis of clots.

By contrast, recent histological evidence of patent, endothelium-linedtracts within pathways created with laser energy supports the assumptionthat the lumen of the laser pathways is or can become hemocompatible andresist occlusion caused by thrombo-activation and/or fibrosis. A thinzone of charring occurs on the periphery of the laser-createdtransmyocardial channels through the well-known thermal effects ofoptical radiation on cardiovascular tissue. This type of interface mayinhibit the immediate activation of the intrinsic clotting mechanismsbecause of the inherent hemocompatibility of carbon. In addition, theprecise cutting action that results from the high absorption and lowscattering of laser energy (CO₂, Ho, etc.) may minimize structuraldamage to collateral tissue, thus limiting the tissuethromboplastin-mediated activation of extrinsic coagulation.

Despite the creation of patent channels and pathways with lasers, thereare reported problems associated with laser TMR procedures. Suchproblems include, in some instances, channel closure which may be causedby selection and use of TMR laser parameters which do not producechannels with the characteristics detected in the histological evidencediscussed above. An additional reported problem encountered in TMRprocedures is adverse effects created by the laser on the diseasedhearts of TMR patients.

U.S. Pat. No. 4,658,817 issued Apr. 21, 1987 to Hardy teaches a methodand apparatus for TMR using a surgical CO₂ laser including a handpiecefor directing a laser beam to a desired location. Hardy suggests thatthe creation of TMR channels using a laser may affect contractility ofthe heart and states that the number of perforations may have to belimited accordingly.

Two subsequent patents, U.S. Pat. Nos. 5,380,316 issued Jan. 10, 1995and 5,389,096 issued Feb. 14, 1995 both to Aita et al., discuss ingeneral methods for intra-operative and percutaneous myocardialrevascularization, respectively. Both patents suggest synchronization ofthe laser with the heart beat is necessary to avoid arrhythmias.

Synchronization of the laser energy delivery with the beating of theheart was also considered an important tool in U.S. Pat. No. 5,125,926issued Jun. 30, 1992 to Rudko et al., reportedly to reduce the chance oflaser induced fibrillation. Rudko et al teaches a heart-synchronizedpulsed laser system for TMR. Utilizing electrical sensing, the heartbeat is monitored using an EKG device. The device automatically deliverswhat appears to be a square pulse of laser energy to the heart only inresponse to electrical detection of a predetermined portion of theheartbeat cycle.

The prior art discussed above suggests that at least some pulsed lasersystems and parameters are potentially damaging to the beating heart orits action and may induce fibrillation or arrhythmia, hence the need forheart synchronization to minimize such effects.

An arrhythmia is a disturbed heart rhythm which often takes over as theprimary rhythm of the heart, as evidenced by a rapid flutter or otherrhythm of the heart muscle, which renders it ineffective at pumpingblood through the vasculature. The process of delivering laser energy totissue results in polarization of individual cells of the heart in thearea of delivery of the laser energy. Polarization of the specializedconducting cells as well as myocardial cells drives the action potentialof cells resulting in responsive contractile motion. Delivering laserenergy can disrupt the normal rhythm of the heartbeat since the cardiacrhythm can be side-tracked to that of the polarized cells as opposed topropagating through the heart along the normal path of the impulse.

The heart's natural, primary pacemaker is found in a group of cellscalled the sinoatrial or sinus node located near the junction of thesuperior vena cava and the right atrium. The electrical impulseoriginates in the endocardium and propagates through the myocardium tothe epicardial surface. The electrical impulse is conducted out of thesinus node to the atria, where it stimulates atrial muscle cells tocontract, and to the atrioventricular node. Upon leaving theatrioventricular node, the electrical impulse continues to propagatedown the conducting system to the bundle of His, into right and leftbranches thereof. The right bundle spreads the electrical impulse to theright ventricle and the left bundle branch propagates the impulse toanterior and posterior positions in the left ventricle to reach thePurkinje fibers. These small fibers form a rapid conduction networkthrough the myocardium to deliver the impulse to all of the individualcontractile muscle cells of the myocardium.

The electrical signal travels at different speeds at different parts ofthe network. While electrical signals on the portion of the networkextending through the atria have been found to travel at velocities ofabout 1 meter per second, these signals slow to about 0.2 m/s as theypass through the atrioventricular node. Signal propagation through theventricular Purkinje network, however, is much faster--approximately 4m/s. Thus, the sinus node is responsible for producing a repeatingelectrical impulse which ultimately causes the muscle cells of the heartto contract in repetitive, wave-like convulsions.

The synchronization solutions proposed in the prior art discussed abovedo not address methods for detecting and compensating for hard todetect, abnormal conduction patterns or rhythms which may occur indamaged hearts. Additionally, EKG monitoring may not detect and allowcompensation for localized or isolated areas of heart tissue which maynot be synchronized with other areas of heart tissue. Excitation of suchisolated areas may cause arrhythmias. In addition to the problemsdiscussed above, heart synchronization as described in the prior artlimits the amount of time the laser can be activated during a heartcycle, thereby increasing the time of a TMR procedure.

A need exists in the prior art for a method and apparatus for performingTMR procedures quickly using specified laser parameters selected tominimize possible cardiac arrhythmias without the need for monitoringthe heart beat.

ADVANTAGES AND SUMMARY OF THE INVENTION

Thus, it is an advantage of the present invention to provide a methodfor performing transmyocardial revascularization (TMR) with laser energyhaving parameters selected to avoid cardiac arrhythmia.

A method for performing transmyocardial revascularization (TMR) withlaser energy having parameters selected to avoid cardiac arrhythmiacomprises the following steps, in combination: determining a wavelengthof the laser energy from a laser selected to perform transmyocardialrevascularization; using the wavelength determination to selectparameters for the laser energy to produce a non-square wave shape;generating the laser energy at the determined wavelength with theselected parameters to produce the non-square wave shape; and deliveringthe generated laser energy in one or more pulses to selected portions ofheart tissue to perform transmyocardial revascularization in myocardiumwithout inducing cardiac arrhythmia and without synchronizing deliveryof the laser energy to a cardiac cycle. In a preferred embodiment, theselected parameters are power level, energy flux, pulse width, and pulsefrequency. In a preferred embodiment, the laser energy has a wavelengthof between about 1.8 and about 2.2 microns, an energy flux of about 1.78J/square millimeter and a power level of at least about 6 watts, thelaser energy being delivered with a pulse frequency of at least about 5Hertz and a pulse width of between about 250 and about 350 millisecond,the laser energy as delivered causing about 5 millimeters lateralnecrosis surrounding a transmyocardial treatment site, and is generatedby a holmium:YAG laser. In a preferred embodiment, the laser energy hasa wavelength of about 0.308 microns, a power level of about 2 watts andan energy flux of between about 2 and about 8 J/square millimeter, andis delivered with a pulse frequency of between about 5 and about 25Hertz and a pulse width of about between about 10 and about 200microseconds, and causes about 5 microns lateral necrosis surroundingthe TMR channel produced thereby, and is generated by a Xe:Cl excimerlaser. In a preferred embodiment, the laser energy has a wavelength ofabout 10.6 microns, an energy flux of about 51 J/square millimeter and apower level at least about 800 watts, is delivered in a single pulseabout of 0.05 seconds and can be gated, and causes between about 0.05 toabout 0.2 millimeters lateral necrosis surrounding a TMR channelproduced thereby, and is generated by a CO₂ laser. In a preferredembodiment, the laser energy has a wavelength of between about 0.488 andabout 0.514 microns, an energy flux of about 1.3-12.74 J/squaremillimeter and a power level at least about 1-10 watts, is delivered ina single pulse, and causes approximately 4 millimeters lateral necrosissurrounding a TMR channel produced thereby, and is generated by an Argonlaser. In a preferred embodiment, the laser energy has a wavelength ofabout 1.06 microns, an energy flux of about 9.5-13 J/square centimeterand a power level at least about 2-100 watts, is delivered with a pulsefrequency of about 1-10 Hertz and a pulse width of about 10 nanoseconds,and causes at least about 15 millimeters lateral necrosis surrounding aTMR channel produced thereby, and is generated by an Nd:YAG laser. In apreferred embodiment, the laser energy has a wavelength of about 2.94microns, an energy flux of about 50-500 J/square millimeter, isdelivered with a pulse frequency of about 1-15 Hertz and a pulse widthof about 1-250 microseconds, and causes about 0.1 millimeters lateralnecrosis surrounding a TMR channel produced thereby, and is generated byan Er:YAG laser.

In a preferred embodiment, the laser energy is delivered to the selectedportions of heart tissue using a catheter apparatus with laser deliverymeans, the method further comprising the following steps: introducingthe catheter apparatus with laser delivery means percutaneously into thevasculature of the patient; and positioning the laser delivery means atthe endocardial surface of the selected portions of heart tissue. In apreferred embodiment, the laser energy is delivered to the selectedportions of heart tissue in a surgical procedure using laser deliverymeans, the method further comprising the following steps: surgicallyaccessing the selected portions of heart tissue; and positioning thelaser delivery means at an epicardial surface of the heart tissue. In apreferred embodiment, assess to the selected portions of heart tissue isachieved from inside a coronary artery. In a preferred embodiment, themethod further including the following step: mechanically piercing theendocardial surface adjacent the selected portions of heart tissue priorto delivering the laser energy into the myocardium. In a preferredembodiment, mechanically piercing the epicardial surface adjacent theselected portions of heart tissue prior to delivering the laser energyinto the myocardium.

It is a further advantage of the present invention to provide a methodfor performing laser-assisted transmyocardial revascularization (TMR)using laser energy with variable parameters selected to avoid cardiacarrhythmia.

The method comprises the following steps, in combination: generatinglaser energy having a non-square wave shape, a selected wavelength, aselected energy flux and a selected power level; and delivering thelaser energy in a plurality of pulses, the plurality of pulses having aselected pulse frequency and a selected pulse width, to selectedportions of myocardium to perform transmyocardial revascularization inmyocardium without cardiac arrhythmia and without synchronizing deliveryof the laser beam with the cardiac cycle. In a preferred embodiment, avariable number of pulses of laser energy is delivered with a variablepulse frequency between about 5 and 20 Hertz. In a preferred embodiment,the laser energy is delivered with a variable pulse repetition rate ofbetween about 1 and 10 pulses. In a preferred embodiment, the laserenergy is delivered with a constant pulse frequency of between about 5and 20 Hertz and a variable pulse repetition rate of between about 1 and10 pulses. In a preferred embodiment, the laser energy is delivered in apulsed mode pulsed at a high repetition rate of fixed frequency, themethod using a laser with an optical shutter and in which the shutter ofthe laser is opened and closed in response to a random sequence ofcommands. In a preferred embodiment, the pulsed laser energy isdelivered in a pulsed mode pulsed at a high repetition rate of fixedfrequency, the method using a laser with a controllable flashlamp and inwhich the flashlamp is allowed to fire only during certain pulses withinthe fixed frequency laser operation in response to a random sequence ofcommands. In a preferred embodiment, the laser energy is delivered in apulsed mode pulsed at a random, variable frequency rate.

It is a further advantage of the present invention to provide a methodof selecting laser parameters for performing laser-assistedtransmyocardial revascularization (TMR) to avoid cardiac arrhythmia andwithout synchronization of delivery of laser energy to a patient'scardiac cycle.

The method comprises the following steps, in combination: selecting aminimum power level of laser energy to be used, the minimum power levelbeing sufficient to ablate heart tissue; setting a pulse frequency asgreat as possible and selected to avoid summation effects; setting apulse width as long as possible and selected to prevent excessively highpeak power without causing undesired levels of thermal damage duringtransmyocardial revascularization; shaping a front end of each pulse oflaser energy to provide non-linear pulses to avoid cardiac arrhythmiaduring transmyocardial revascularization; and correcting the selectedpower level, pulse width, pulse frequency, pulse width, and shaping formechanical events. In a preferred embodiment, the selected parametersare a single pulse, power level, energy flux, and pulse width.

Numerous other advantages and features of the present invention willbecome readily apparent from the following detailed description of theinvention and the embodiments thereof, from the claims and from theaccompanying drawings in which the details of the invention are fullyand completely disclosed as a part of this specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C are graphical representations of the process of summation.

FIGS. 2A and 2B are graphical comparisons of the resultant differencebetween ablation with a square wave versus ablation with a non-squarewave.

FIG. 3 is a flow chart demonstrating a method of selecting and settingvariable laser parameters.

FIG. 4 is a representative example of variable laser parameters.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

This invention teaches laser parameters which, in optimizedcombinations, reduce or eliminate the risk of inducing arrhythmia whileperforming a laser-assisted TMR. The methods described herein do notrequire cardiac monitoring or any other form of synchronization of laserdelivery with the natural cardiac rhythm.

The present invention is intended for use with any medical laser. Inparticular, excimer and Holmium lasers, including many of variousdifferent types known and available now or at any time, are particularlysuited to the present invention. However, any suitable laser source,pulsed or otherwise, may be used to provide laser energy to the laserdelivery means of the present invention for performing the method of thepresent invention. Other laser sources include but are not limited toCO₂, argon, neodymium: yttrium aluminum garnet (Nd:YAG) as well aserbium: yttrium aluminum garnet (Er:YAG). The following laser operatingparameters have been determined to be optimal parameters for performinglaser-assisted TMR without causing arrhythmias.

    __________________________________________________________________________    Laser Operating Parameters                                                           Xe:Cl                                                                  Type   excimer Ho:YAG CO.sub.2                                                                             Argon  Nd:YAG Er:YAG                             __________________________________________________________________________    Wavelength                                                                           0.308 μm                                                                           2.1 μm                                                                            10.6 μm                                                                           0.488- 1.06 μm                                                                           2.94 μm                                                      0.514 μm                                      Pulse  5-20 Hz ≧5 Hz                                                                         Single pulse,                                                                        CW-    1-10 Hz;                                                                             1-15 Hz                            frequency             CW, can be                                                                           multimode,                                                                           CW or                                                           superpulsed                                                                          can be q-                                                                            pulsed (CW                                                             switched                                                                             can be                                                                 or "gated"                                                                           "gated")                                  Energy flux                                                                          about 45-60                                                                           about 1.78                                                                           about 51                                                                             about 1.3-                                                                           about 9.5-                                                                           about 50-                                 mJ/mm.sup.2                                                                           J/mm.sup.2                                                                           J/mm.sup.2                                                                           12.75  13 J/cm.sup.2                                                                        500 J/mm.sup.2                                                  J/mm.sup.2                                                                           pulsed;                                                                       about 8-27                                                                    J/mm.sup.2 CW                             Pulse width                                                                          about 20-200                                                                          about 250-                                                                           about 0.05 s                                                                         N/A    10 n sec,                                                                            approx 1-                                 ns or more                                                                            350 μs            CW or  250 μsec                                                            pulsed                                    Wave shape                                                                           Non-square                                                                            Non-square                                                                           Non-square                                                                           N/A    Non-square                                Power  about 2 W                                                                             about ≧6 W                                                                    800 W  1-10 W 2-100 W                                   Lateral                                                                              about 5 μm                                                                         about 0.5                                                                            about 0.05-                                                                          about ≧4                                                                      about ≧15                                                                     about .025-                        necrosis       mm     0.2 mm mm     mm 0   0.1 mm                                                                 switched                                                                      10-15 μm                               __________________________________________________________________________

The above laser operating parameters for various types of lasers wereselected to enable laser energy to smoothly and gradually interact withthe tissue of the heart thereby avoiding, where possible, sharp andsudden tissue interaction. A contoured, smooth, gradual application ofenergy will provide less shock to the heart itself. A non-square wavewith a relatively shorter pulse width generally is preferred to achievesuch smooth and gradual tissue interaction. It will be recognized bythose skilled in the art that achieving the desire effect requiresvariation of the individual elements of the laser operating parametersdepending upon the type of laser selected. Each laser operatingparameter is discussed separately below.

WAVELENGTH

It is recognized that numerous medical lasers having differentwavelengths are currently available. Selection of an appropriatewavelength depends at least in part upon the tissue to be treated withthe laser. For TMR, the mechanism of delivering laser energy to thewater component of heart tissue to effect ablation and channeling highlyefficient. Mid-infrared lasers, such as the 2.1 micron wavelengthholmium:YAG laser, are well suited for cutting and ablating heart tissuebecause, in general, wavelengths longer than approximately 1.4 micronsare highly absorbed by water. It is by means of this strong absorptionin water that mid-infrared laser energy is converted to heat energy intissue.

If the energy density in the tissue is high enough, the tissuevaporizes. Since water is the primary constituent of most soft tissue,about 80% or more, the correlation is fairly accurate, although therewill be minor differences between absorption of mid-infrared energy inwater and in tissue, as well as between different types of tissue. Themid-infrared absorption spectrum of water is well known and absorptioncoefficients over a larger range are available.

The absorption coefficient a of the 2.1 micron holmium.YAG laser isabout 26 cm⁻¹. This modality is highly efficacious for cutting andablating. For comparison, the absorption coefficients of the 1.06 micronwavelength energy created by the neodymium:YAG laser and the 10.6 micronradiation produced by a CO₂ laser are 0.13 and 823 cm⁻¹, respectively.The inverse of the absorption coefficient is directly correlated withenergy absorption depth d:

    d=1/α

A large absorption coefficient implies a short penetration depth.Penetration is short because the energy is immediately absorbed by thecells closest to the source and does not extend into the tissue.

Other lasers include the Xe:Cl excimer laser which delivers energy at0.308 μm, the argon laser which delivers energy at between about0.488-0.514 Aim, the CO₂ laser which delivers energy at 10.6 μm, and theNd:YAG laser which delivers energy at 1.06 μm.

CO₂ lasers used in a fluid environment in near-contact procedures,despite a relatively short penetration depth, have the disadvantage inthat even a thin film of water between the fiber and the tissue willgreatly diminish the effective laser power because of the largeabsorption coefficient. Hence, the use of gas insufflation is generallyrequired with the CO₂ laser. Furthermore, CO₂ lasers generally requirefurther manipulation of parameters to create TMR channels.

In selecting a particular wavelength for a laser, and adjustingparameters to compensate for differences in absorption by the tissue, itis important to consider the need to achieve an end result of anon-square wave.

PULSE WIDTH AND FREQUENCY

To prevent electrical arrhythmia of the heart during TMR it has beenfound that certain shorter pulse widths not only assure minimal andpredictable thermal damage to surrounding tissue but are less likely tointerfere with the cardiac signal which may lead to arrhythmia. Byreducing the interval between pulses to significantly shorter than theinterval of a beating heart at approximately 60 beats per minute, or 1beat per second (1 hertz), there is much less chance that a single laserpulse will side track the electrical rhythm and take over propagation ofthe electrical impulse throughout the heart. Furthermore, higherfrequencies create a hole faster thereby reducing the probability that alaser polarized group of cells in the area of channel creation willshort circuit a heartbeat signal. In a preferred embodiment of themethod of the present invention, pulse widths less than about 300milliseconds, and preferably lower than about 200 milliseconds, havebeen found to be most effective. Thus, in a preferred embodiment of themethod of the present invention, frequency rates greater than 5 hertzand preferably between about 5 hertz and about 25 hertz are least likelyto induce electrical arrhythmia during TMR.

The holmium:YAG or other comparable pulsed laser can be pulsed at acertain rate or within a range of rates. Pulsed application of laserenergy to effect vaporization and ablation of the tissue has beendemonstrated to be preferable in some instances to application of laserenergy in a single pulse. In delivering energy to tissue, a given volumeof tissue will absorb laser energy converting it into heat. To ablate agiven "target" volume of tissue it is necessary to put enough heatenergy into the volume to vaporize it. A certain minimum rate ofdelivery of energy is required to counteract the effect of "thermalrelaxation" which is the phenomenon by which heat diffuses out of theheated volume of tissue. The "thermal relaxation time" τ is defined asthe amount of time required for a given amount of heat to diffuse out ofa given volume of tissue. Based upon an estimation that the thermaldiffusivity of tissue is very close to that of water, and usingclassical heat transfer theory, the thermal relaxation time period for aspot size of tissue using a 400 micron diameter fiber in contact or veryclose proximity to the tissue has been calculated to be betweenapproximately 57 and 286 milliseconds using the following equation:

    1/τ˜4α.sup.2 K+16K/d.sup.2

where K=thermal diffusivity of tissue, d=diameter of the illuminatedspot. The calculation is based on the estimate that K˜1.4×10⁻³ cm⁻² /s.

In general, the pulse width must be optimized to prevent a peak powerspike while achieving a predetermined energy flux for ablation or anyother procedure. Too short a duration will require too sharp an energyspike with a very high peak power level. On the other hand, too long apulse will result in summation of energy effects which result inoverheating, an increased zone of thermal necrosis, and possible othercoagulation type effects.

It will be understood that the Nd:YAG, Ho:YAG, Xe:Cl excimer and Er:YAGlasers are all pulsed lasers in at least preferred forms, and thereforeoptimum pulse widths may be selected. Appropriate pulsing will avoidsummation effects and will provide a contoured, gentle leading edge ofthe energy delivery profile.

Use of a continuous wave laser, such as argon, some Nd:YAG and some CO₂lasers, typically can be enhanced by mechanically chopping thecontinuous wave to reduce unfavorable thermal effects. The advantage tochopping such laser beams is to reduce or eliminate adverse summationeffects on the tissue. However, mechanically chopping a continuous wavedoes make it more difficult to achieve a non-square or otherwise lessassaultive delivery of laser energy. In any event, as discussed below,whether delivering pulsed energy or continuous wave energy, the rate atwhich it is delivered is also important. Too narrow of a pulse width attoo low of a power level will fail to create patent channels. Thus, thepower of the laser beam, or the amount of energy delivered to the tissuein terms of Joules per second, is also an important factor to consider.

In general, optimal pulse frequencies and pulse widths to avoidarrhythmias combine to create a relatively narrow pulse width deliveredat a relatively high pulse frequency.

ENERGY FLUX AND POWER

Energy flux E_(pulse) or fluence, also referred to as "radiant exposure"or energy density, is expressed in units of pulse energy per area, orjoules per square centimeter. The "threshold radiant exposure" F_(th) isdefined as the single pulse threshold for the ablation of biologictissue. For radiant exposures less than this threshold, tissue is notvaporized or ablated, but, instead, is heated. For radiant exposureshigher than this threshold, tissue is vaporized. Thus, for effectiveablation, the energy per pulse divided by the area of the spot size mustbe greater than the threshold radiant exposure.

    E.sub.pulse A>F.sub.th

As an approximation, the threshold energy per unit volume for water isknown to be 2500 joules per cubic centimeter. This is also the heat ofvaporization, or the heat required to raise one cubic centimeter fromabout body temperature to steam at 100 degrees centigrade. Thisthreshold energy per unit volume is given by the equations:

    F.sub.th ×α or F.sub.th /d

Depth of penetration, discussed above, is equal to the inverse of theabsorption coefficient and the threshold radiant exposure for biologictissue is about 100 joules per square centimeter. An effective energyflux must be at least this great. Experimentally, threshold energy fluxrates of between about 5 and 75 joules per square centimeter are found.

The average power P_(av) of a repetitively pulsed laser is equal to theenergy per pulse times the number of pulses per unit time (P_(ay)=joules/pulse×pulses/second, in watts). The number of tissue parcelsablated per second is equal to the repetition rate of the laser inpulses per second, or hertz. Thus, increasing the pulse repetition rateto increase the average power delivered to the tissue linearly increasesthe rate of tissue removal.

If a region of tissue is illuminated by more than one pulse, an excessof energy accumulates in the tissue. For example, if the individualpulse energy and spot size provide an energy flux below the single pulsethreshold radiant exposure F but the interval between pulses at aparticular repetition rate is shorter than the characteristic thermalrelaxation time τ, a parcel or given volume of tissue may be ablatedafter a number of pulses has impinged the tissue. This process isreferred to as summation.

FIGS. 1A-1C are graphical representations of the process of summation.In FIG. 1A, an initial pulse of energy 80 increases the temperature (T)of the tissue locally. However, given a large amount of time (t) betweenpulses, the temperature of the tissue drops rapidly and immediately at82 during the beginning of the delay period (D) following irradiationwith no net result. Referring now to FIG. 1B, decreasing the timebetween pulses results in a positive net result and tissue ablation. Aninitial pulse of energy 84 increases the local temperature to a certainpoint 86, and then the temperature begins to drop during the time period88 immediately following the first irradiation step. At an intermediatetemperature level 90, another pulse of laser energy is delivered toimpinge upon the tissue. The additional pulse elevates the temperaturefrom temperature level 90 to a temperature 91 which is high enough tocause ablation. Repeated cycling as in FIG. 1B is very effective atachieving ablation without causing excess thermal damage in thesurrounding tissue. During this mode of operation, the system can bedescribed with the following equation:

    (P.sub.av /A)-(F.sub.th /τ)>0

(It should be noted that F_(th) may not remain constant in this regime:only the first pulse encounters fully hydrated, native tissue at bodytemperature.) Effectively, this criterion indicates that ablation cangenerally take place only if energy is supplied faster than it diffusesaway. Because the thermal relaxation time τ is between 57 and 286milliseconds, the interval between pulses can be as short as between 20and 50 milliseconds, which is shorter than the shortest thermalrelaxation time that arises from laser interaction with biologic tissue.A repetition rate greater than 3.5 hertz will permit entry into thisFIG. 1B regime, however, as described above, pulse frequencies ofbetween 5 and 15 hertz are optimum for laser-assisted TMR in which therisk of electrical arrhythmia is optimally reduced. Using theseparameters, an average power delivery will be greater than 6 watts, or 6joules per second.

By further decreasing the period between laser pulses, an excess of heatbuilds up in the tissue as shown in FIG. 1C. After an initialtemperature rise 92 and a brief period of thermal diffusion 94, afurther pulse of energy 96 will continue to drive the temperature of thetissue upwards. Not only is this an inefficient modality forrevascularization, but the risk of thermal runaway and associatedthermal damage to surrounding tissue is very great. Additionally, anelevated temperature and excessive tissue damage will both tend toincrease the risk of arrhythmia. Not only are the cells which areelevated in temperature more easily depolarized, as they lie in a periodof relative refractivity, but thermal damage to cells also interfereswith their normal firing and propagation of the electrical impulse.

Therefore, in general, the power of the laser used, or the rate ofdelivery of energy to the tissue, can be tailored to avoid collateraldamage of subsequent pulses. Though summation and overheating are moreof a problem with continuous wave lasers, too small a pulse width withtoo high a peak-power pulse with lasers such as the Xe:Cl excimer,though at relatively similar powers as other pulsed lasers, may alsohave a harmful, explosive result.

In summary, depending upon the laser selected, the energy flux and powerparameters should be adjusted to ensure ablation without deleterioussummation effects. The net result of such optimization is a reduction inthe incidence of arrhythmia during TMR or other laser procedure.

WAVE SHAPE

As has been stated, adjustment of the parameters discussed above isdesigned to create a non-square wave for TMR and other laserapplications. There is a direct correlation between likelihood ofarrhythmia and wave shape. When TMR is performed using a wave with a"square" shape, that is, a wave which immediately and linearly increasesto a near-maximum level, continues at that level until dropping sharplyback to the lower level. A non-square wave would be one that isnon-linear and had a more gradual increase in amplitude, or curve with arelatively lower slope, with a subsequent gradual decrease. Pastexperiences with square wave lasers in coronary and TMR applicationsclearly demonstrate that the square waveform is more explosive andtraumatic to the heart. A comparable energy wave with a Gaussian,bell-shaped or other shaped waveform does not have a tendency to createarrhythmias whereas square waveforms have a greater tendency to inducearrhythmia due to a resulting shock wave which adversely impacts theentire heart.

FIGS. 2A and 2B are graphical comparisons of the resultant differencebetween ablation with a square wave versus ablation with a non-squarewave. In both plots, the vertical axis corresponds to both thetemperature of individual cells in the volume of tissue heated by asingle pulse as well as the energy level of those individual cells. InFIG. 2A, when a square-wave pulse is applied to the tissue, thetemperature of the tissue rises sharply during the period between t₀ andt₁. As the population density of individual cells heated above thethreshold temperature T_(th) up to a maximum temperature T_(max) isrelatively large, the chance that one individual cell might depolarizeand take over or "capture" the rhythm of the heart is increased. Thesecells at risk of taking over the heart rate and causing an arrhythmiaare identified by the shaded portion of the graph 100. A largepopulation of cells rapidly depolarize and any one can serve as a situsof arrhythmic activity. When the pulse of laser energy is non-squareshaped as in FIG. 2B, the statistical probability that a single cell inthe population of cells between T_(th) and T_(max) might capture theelectrical cycle and become arrhythmic is much less. Assuming that athreshold temperature T_(th) exists above which temperature individualcells may become depolarized (but below which the risk is very small),the area 102 under the non-square, generally bell-shaped curve in FIG.2B is much smaller than area 100. It will be understood that the shadedareas under the curves above the threshold temperature levels generallyare proportional to the probability that arrhythmia will beproduced--the smaller the area the less likelihood of inducing anarrhythmic cardiac cycle. Thus, the areas 104 and 106 can be said to beproportional in magnitude to the decrease in likelihood that an errantdepolarized cell will capture the cardiac cycle and cause arrhythmia.

The net effect of providing a non-square shaped pulse wave is to causethe same amount of ablation, perhaps over a slightly longer period oftime, with a decreased risk of inducing arrhythmia. Bell orGaussian-shaped waveforms have are highly effective at channeling in theTMR procedure and the risk of inducing arrhythmia is optimallyminimized.

It is demonstrated that a non-square, contoured wave shape will tend toreduce the risk of causing arrhythmia in TMR patients. This is generallydifficult to achieve with continuous wave lasers since chopping of a CWlaser beam will not avoid a square or otherwise fairly sharp wave front.However, using pulsed lasers, optimization of a contoured wave willfurther eliminate a high peak-power spike at or near the center of thepulse. Such optimization will include adjustment of the other parametersdiscussed above.

ZONE OF LATERAL NECROSIS

While the precise influence of thermal injury on TMR channel patency, orother desirable TMR result, is unclear, the extent of lateral thermalnecrosis should be controlled by careful selection of the laser and itsoperating parameters. In general, minimizing lateral tissue necrosiswill result in more efficient tissue removal from the channel itself,and will also result in minimal trauma to surrounding tissue. Althoughlateral tissue damage may be sought in some applications, in general,minimal trauma to surrounding tissues is a desirable goal.

CO₂ lasers have been found to produce an intense inflammatory responsewhich may be inconsistent with provision and promotion of an alternativecirculation, one of the therapeutic mechanisms believed to be associatedwith TMR. Although mechanically-formed channels were completely occludedwithin 2 days of formation by cellular infiltrate, eventually formingscar tissue, many laser created channels remain patent for a longerperiod of time, but too may become occluded with fibroblasts,macrophages and subsequently collagen.

Thermal injury to myocardium surrounding channels may delay healing andthus increase duration of patency, though the lack of an obvious,visibly patent channel may not preclude blood flow in vivo via thechannels. However, it has been shown that it is possible to alter thedegree of thermal injury, for example with the Ho:YAG laser, by changingpulse energy or repetition rate. It has also been shown that with lasercreated channels, the extent of tissue damage associated with thecreation of the channels can be reflected in the degree of fibrosisproduced. Fibrosis associated with the initial injury results indisorganization of adjacent myocytes. The observed disarray is similarto that found in viable muscle adjacent to a healed infarct. Hence thedegree of muscle disorganization may be determined by the amount ofchannel-associated fibrosis.

The above described structural changes due to lateral thermal necrosisresult in diminished heart function and also provide a substrate forabnormal electrical conduction. This may increase the chance of inducingarrhythmia during such procedure. An increase in interstitial collagencan be expected to affect heart function by decreasing contractility,elasticity and pumping strength, and can also be expected to decreasecell-to-cell contact.

Thus, in general, at least a minimum degree of thermal necrosis will bepresent and is considered beneficial. An excess of lateral necrosis,however, should be avoided since too great an amount of thermal injurywill cause other complications non-beneficial to the TMR patient.

MISCELLANEOUS PARAMETERS

Another cause of tissue damage is the production of vapor bubbles in thetissue being ablated with lasers. The degree of myocardial disruption bysuch "acoustic" injury is slight at repetition rates of between about 2and 3 Hertz, but vapor bubble effect may increase tissue injury inexcess of that caused by temperature increases.

An additional consideration will be the temperature of the heart itself.In TMR procedures, cooling the heart will help prevent an accumulationof undesirable, potentially harmful heat. In other words, summationeffects can be minimized by applying external cooling to the heartitself or portions thereof, selectively or over large areas orotherwise, to effectively increase, by as much as several fold or more,the thermal relaxation time for the tissue.

VARIABLE PARAMETERS

The above discussion demonstrates various parameters for different laserenergies chosen to minimize the possibility of arrhythmias and is basedupon a generally constant, regular delivery of laser energy using thoseparameters. Arrhythmias also may be prevented by providing variable, ornon-synchronous, delivery of laser energy. Non-synchronous TMRprocedures lessen the chance of capture of the heartbeat because the TMRprocedure does not use a predictable, constant firing sequence for theheart to follow.

FIG. 3 is a block diagram of a preferred embodiment of a method fornon-synchronous laser-assisted TMR using variable parameters. Providingvariable laser parameters further decreases the risk that surroundingtissue will abandon the regular pattern of the heart beat to follow theparticular laser parameters used in the laser TMR procedure. Thefollowing table illustrates several variable laser parameters which maybe used to create TMR pathways with decreased risks of arrhythmias.

    __________________________________________________________________________              Variable Parameters                                                           MODE                                                                                      CONSTANT NUMBER OF                                                                          FIXED PULSE                                         VARIABLE NUMBER                                                                           PULSES DELIVERED/                                                                           REPETITION RATE,                                    OF RANDOMLY VARIABLE PULSE                                                                              PULSES GATED                              PULSE TRAIN                                                                             CHANGING PULSES                                                                           REPETITION RATE                                                                             RANDOMLY                                  __________________________________________________________________________    PULSE TRAIN #1                                                                           2 pulses    2 pulses      2 pulses                                            5 hertz     5 hertz      15 hertz                                             7 watts     7 watts       7 watts                                  PULSE TRAIN #2                                                                           3 pulses    2 pulses      3 pulses                                           15 hertz    10 hertz      15 hertz                                             7 watts     7 watts       0 watts = OFF                            PULSE TRAIN #3                                                                           1 pulse     2 pulses      3 pulses                                            8 hertz    15 hertz      15 hertz                                             7 watts     7 watts       7 watts                                  PULSE TRAIN #4                                                                           2 pulses    2 pulses      1 pulses                                            6 hertz     8 hertz      15 hertz                                             7 watts     7 watts       0 watts = OFF                            PULSE TRAIN #5                       6 pulses                                                                     15 hertz                                                                       7 watts                                  __________________________________________________________________________

The variable parameters may be preset at the laser console controlpanel. As shown, the laser energy applied to the heart muscle in a TMRprocedure is varied by providing (1) a variable number of pulses at arandomly changing pulse repetition rate, (2) a constant number of pulsesdelivered at variable pulse repetition rates, or (3) randomly gatedpulse delivery at a fixed repetition rate. Mechanical or directmodulation may be used to vary the gating. Mechanical modulation ispreferred using a mechanical device such as an automatic shutter or beamchopper.

FIG. 4 is a representation of beam patterns which are possible using thevariable laser parameter method of the present invention. One method ofcreating "random" frequency pulses is to provide an intracavity beamshutter. The laser is pulsed at a high repetition rate of fixedinterval, for example 15-20 hertz. The system's central processing unit(CPU) or computer contains a pre-programmed random sequence of commandsto open the shutter for a "random" period of time, and close the shutterfor a "random" period of time until the foot switch is released. Thus,line 200 represents the fixed interval pulse rate of the laser. This isa constant rate, for example 15-20 hertz. Line 210 represents thecontroller's shutter operation. It is seen that the actual laser outputduring this time will be controlled in an on and off mannerautomatically by the operating program of the system CPU or otherprocessor. Line 220 is representative of the actual output of the laser,allowing pulses of laser energy to be emitted during the "on" periodsand suspending laser emission past the shutter during the "off" periods.

A second novel method for producing a variable laser output pattern isto control the flashlamp of the laser as opposed to a mechanicalshutter. As with the mechanical intra-cavity shutter, the laser ispulsed at a fixed repetition rate of, typically, 15-20 hertz. Thesystem's CPU contains a pre-programmed randomized sequence of commandsto allow the flashlamp driver to fire only during certain pulses withthe fixed repetition rate. A pattern similar to that shown in line 220is possible in this manner.

A third method for producing a variable laser output is to control theflashlamp directly. Instead of maintaining a continuous fixed repetitionrate, of which only certain pulses are allowed to occur, this methoduses a pre-programmed memory of variable repetition rates between about5 and 20 hertz continuously delivered to tissue until the foot switch isreleased. This resultant beam pattern is depicted in line 230, a randompattern.

Yet a fourth method for producing a variable laser output is to changethe repetition rate after a predetermined set number of pulses have beendelivered. For example, the pattern shown in line 240 is a set of 2individual pulses per each pulse repetition rate used. The randomvariation of repetition rate changes after each 2 pulse set, as shown inline 250 where the number of pulses per second is shown. The resultantbeam pattern is depicted in line 260, a random pattern.

METHOD FOR SELECTING OPTIMUM PARAMETERS

Based on the foregoing, a preferred method for determining the optimumparameters for performing TMR utilizing any suitable medical laseravailable will be apparent. At the outset, an initial consideration isto minimize the total amount of energy utilized to complete theprocedure. Adapting parameters to this consideration will decrease theoverall trauma to the heart and minimize the risk of inducingarrhythmia. A power setting which eliminates potential linear effectssuch as short, explosively high peak, power pulses will be moredesirable.

Additionally, when using a pulsed laser, which is in general moredesirable than a continuous wave laser, increasing the pulse width, toprevent an excessively high peak power, to deliver a predeterminedamount of energy in a given pulse, up to the point of thermal damagecaused by summation effects, is desirable. In other words, the thermalrelaxation time and factors which might affect that value including, butnot limited to, heart temperature, will be considered.

Furthermore, contouring or shaping the front end of the wave form toprovide an efficient cutting or ablation wave shape but to preventexplosive, linear square wave shapes. Again, avoiding an excessivelyhigh peak power spike within the pulse will be advantageous.

Finally, correcting for mechanical events inherent in the selected TMRsystem, including but not limited to the elected access to the heart,duration of the entire procedure, manipulation of the laser deliverymeans and movement of the beating heart; and, mechanical events inherentin the individual patient, including but not limited to heart geometry,pre-existing heart arrhythmia or other factors causing a predispositionto such.

The present invention is intended for use with any medical laser. Inparticular, the Holmium or excimer laser is particularly suited to thepresent invention. However, any suitable laser source, pulsed orotherwise, could provide laser energy to the laser delivery means of thepresent invention for performing the method of the present invention.Likewise, the catheter and surgical equipment, including laser deliverymeans, referred to in the present document as well as that known andused in medicine and other disciplines today and in the future, will beincluded in the scope of this disclosure. Such laser delivery meansinclude, but are not limited to, individual optical fibers as well asbundles of fibers, rods, mirrors configurations and other laser deliverymeans with and without focusing lens and the like. It will also beunderstood that the apparatus and method of the present invention asdescribed herein, including the novel combinations or use with anyconventional mechanism or method which are known to those skilled in theart, are included within the scope of this invention.

It will further be understood that while the present invention has beendescribed for performing TMR on endocardial surfaces in the leftventricle, the apparatus and methods described herein are equallyintended for use in any suitable procedure, including but not limited toprocedures where any device need be extended through a guiding catheterto an opening or other point within the body for other medicalprocedures including laser treatment, visualization, biopsy, etc."Stimulation", for example, is performed by using laser energy to createzones or pockets, optionally interconnected at least initially by smallchannels ablated through the tissue, for the introduction of blood borngrowth and healing factors and stimulated capillary growth surroundingthe lased zones or pockets to create an increased supply of oxygen tothe tissue and thus a revitalization of the heart muscle. Methods andapparatus for causing stimulation are more fully described in co-pendingU.S. patent application Ser. No. 08/664,956 filed, allowed.

While the principles of the invention have been made clear inillustrative embodiments, there will be immediately obvious to thoseskilled in the art many modifications of structure, arrangement,proportions, the elements, materials, and components used in thepractice of the invention, and otherwise, which are particularly adaptedto specific environments and operative requirements without departingfrom those principles. The appended claims are intended to cover andembrace any and all such modifications, with the limits only of the truespirit and scope of the invention.

We claim:
 1. A method for performing transmyocardial revascularization(TMR) with laser energy having parameters selected to avoid cardiacarrhythmia, the method comprising the following steps, incombination:determining a wavelength of the laser energy from a laserselected to perform transmyocardial revascularization; using thewavelength determination to select parameters for the laser energy toproduce a non-square wave shape; generating the laser energy at thedetermined wavelength with the selected parameters to produce thenon-square wave shape; and delivering the generated laser energy in oneor more pulses to selected portions of heart tissue to performtransmyocardial revascularization in myocardium to avoid cardiacarrhythmia and need for synchronizing delivery of the laser energy to acardiac cycle.
 2. The method of claim 1 wherein the selected parametersare power level, energy flux, pulse width, and pulse frequency.
 3. Themethod of claim 2 wherein the laser energy has a wavelength of betweenabout 1.8 and about 2.2 microns, an energy flux of about 1.78 J/squaremillimeter and a power level of at least about 6 watts, the laser energybeing delivered with a pulse frequency of at least about 5 Hertz and apulse width of between about 250 and about 350 milliseconds, the laserenergy as delivered causing about 5 millimeters lateral necrosissurrounding a transmyocardial treatment site.
 4. The method of claim 3wherein the laser energy is generated by a holmium:YAG laser.
 5. Themethod of claim 2 wherein the laser energy has a wavelength of about0.308 microns, a power level of about 2 watts and an energy flux ofbetween about 2 and about 8 J/square millimeter, and is delivered with apulse frequency of between about 5 and about 25 Hertz and a pulse widthof about between about 10 and about 200 microseconds, and causes about 5microns lateral necrosis surrounding the TMR channel produced thereby.6. The method of claim 5 wherein the laser energy is generated by aXe:Cl excimer laser.
 7. The method of claim 2 wherein the laser energyhas a wavelength of about 10.6 microns, an energy flux of about 51J/square millimeter and a power level at least about 800 watts, isdelivered in a single pulse about of 0.05 seconds and can be gated, andcauses between about 0.05 to about 0.2 millimeters lateral necrosissurrounding a TMR channel produced thereby.
 8. The method of claim 7wherein the laser energy is generated by a CO₂ laser.
 9. The method ofclaim 2 wherein the laser energy has a wavelength of between about 0.488and about 0.514 microns, an energy flux of between about 1.3 and about12.74 J/square millimeter and a power level at least between about 1 andabout 10 watts, is delivered in a single pulse, and causes approximately4 millimeters lateral necrosis surrounding a TMR channel producedthereby.
 10. The method of claim 9 wherein the laser energy is generatedby an Argon laser.
 11. The method of claim 2 wherein the laser energyhas a wavelength of about 1.06 microns, an energy flux of between about9.5 and about 13 J/square centimeter and a power level at least betweenabout 2 and about 100 watts, is delivered with a pulse frequency ofbetween about 1 and about 10 Hertz and a pulse width of about 10nanoseconds, and causes at least about 15 millimeters lateral necrosissurrounding a TMR channel produced thereby.
 12. The method of claim 11wherein the laser energy is generated by an Nd:YAG laser.
 13. The methodof claim 2 wherein the laser energy has a wavelength of about 2.94microns, an energy flux of between about 50 and about 500 J/squaremillimeter, is delivered with a pulse frequency of between about 1 andabout 15 Hertz and a pulse width of between about 1 and about 250microseconds, and causes about 0.1 millimeters lateral necrosissurrounding a TMR channel produced thereby.
 14. The method of claim 13wherein the laser energy is generated by an Er:YAG laser.
 15. The methodof claim 1 wherein the laser energy is delivered to the selectedportions of heart tissue using a catheter apparatus with laser deliverymeans, the method further comprising the following steps:introducing thecatheter apparatus with laser delivery means percutaneously into thevasculature of the patient; and positioning the laser delivery means atthe endocardial surface of the selected portions of heart tissue. 16.The method of claim 15 further including the following step:mechanicallypiercing the endocardial surface adjacent the selected portions of hearttissue prior to delivering the laser energy into the myocardium.
 17. Themethod of claim 1 wherein the laser energy is delivered to the selectedportions of heart tissue in a surgical procedure using laser deliverymeans, the method further comprising the following steps:surgicallyaccessing the selected portions of heart tissue; and positioning thelaser delivery means at an epicardial surface of the heart tissue. 18.The method of claim 17 further including the following step:mechanicallypiercing the epicardial surface adjacent the selected portions of hearttissue prior to delivering the laser energy into the myocardium.
 19. Themethod of claim 1 wherein access to the selected portions of hearttissue is achieved from inside a coronary artery.
 20. A method forperforming laser-assisted transmyocardial revascularization (TMR) usinglaser energy with variable parameters selected to avoid cardiacarrhythmia, the method comprising the following steps, incombination:generating laser energy having a non-square wave shape, aselected wavelength, a selected energy flux and a selected power level;and delivering the laser energy in a plurality of pulses, the pluralityof pulses having a selected pulse frequency and a selected pulse width,to selected portions of myocardium to perform transmyocardialrevascularization in myocardium to avoid cardiac arrhythmia and withoutneed for synchronizing delivery of the laser beam with the cardiaccycle.
 21. The method of claim 20 in which a variable number of pulsesof laser energy is delivered with a variable pulse frequency betweenabout 5 and 20 Hertz.
 22. The method of claim 20 in which the laserenergy is delivered with a variable pulse repetition rate of betweenabout 1 and 10 pulses.
 23. The method of claim 20 in which the laserenergy is delivered with a constant pulse frequency of between about 5and 20 Hertz and a variable pulse repetition rate of between about 1 and10 pulses.
 24. The method of claim 20 in which the laser energy isdelivered in a pulsed mode pulsed at a high repetition rate of fixedfrequency, the method using a laser with an optical shutter and in whichthe shutter of the laser is opened and closed in response to a randomsequence of commands.
 25. The method of claim 20 in which the pulsedlaser energy is delivered in a pulsed mode pulsed at a high repetitionrate of fixed frequency, the method using a laser with a controllableflashlamp and in which the flashlamp is allowed to fire only duringcertain pulses within the fixed frequency laser operation in response toa random sequence of commands.
 26. The method of claim 20 in which thelaser energy is delivered in a pulsed mode pulsed at a random, variablefrequency rate.
 27. A method of selecting laser parameters forperforming laser-assisted transmyocardial revascularization (TMR) toavoid cardiac arrhythmia and without need for synchronization ofdelivery of laser energy to a patient's cardiac cycle, the methodcomprising the following steps, in combination:selecting a minimum powerlevel of laser energy to be used, the minimum power level beingsufficient to ablate heart tissue; setting a pulse frequency as great aspossible and selected to avoid summation effects; setting a pulse widthas long as possible and selected to prevent excessively high peak powerwithout causing undesired levels of thermal damage duringtransmyocardial revascularization; shaping a front end of each pulse oflaser energy to provide non-linear pulses to avoid cardiac arrhythmiaduring transmyocardial revascularization; and correcting the selectedpower level, pulse width, pulse frequency, and shaping for mechanicalevents.
 28. The method of claim 1 wherein the selected parameters are asingle pulse, power level, energy flux, and pulse width.